IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Polyamine metabolism and autophagy in the Trypanosoma cruzi‐host cell interplay
Autor/es:
ROMANO PATRICIA SILVIA
Lugar:
Buenos Aires
Reunión:
Conferencia; Buenos Aires Conferences 2013; 2013
Institución organizadora:
Facultad de Medicina. Universidad de Buenos Aires
Resumen:
Autophagy is a cell process implicated in many physiological and pathological
situations, even during the infection by intracellular pathogens. Although many compounds
are currently used to modulate autophagy, many of them are nonspecific and potentially
toxic. Recently it was demonstrated that the polyamine spermidine is a physiological inducer
of autophagy. Otherwise, autophagy induction significantly increases host cell colonization by
T. cruzi, the etiological agent of Chagas disease. In this study we have characterized the effect
of polyamine depletion on autophagy and T. cruzi infectivity. Our data show that spermidine
depletion by treatment of cells with the ornithine decarboxylase inhibitor
difluoromethylornithine (DFMO) suppressed the autophagic response to starvation and
rapamycin treatment. This effect was associated with a decrease in the levels of the
autophagic proteins LC3 and ATG5. Moreover, as a consequence of inhibiting host cell
autophagy, DFMO impaired T. cruzi infection under autophagy induced or even control
conditions. Thus, our results point to DFMO as a novel autophagy inhibitor that may have
value in limiting autophagy and the spread of the infection in Chagas disease and possibly
other pathological settings.